muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 8

disease
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Also known as LGMD-POMGNT2 related myopathyMDDGC8

Summary

muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 8 (MONDO:0029135) is a disease with 1 cohort gene.

At a glance

  • Cohort genes: 1
  • ClinVar variants: 14

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namemuscular dystrophy-dystroglycanopathy (limb-girdle), type C, 8
Mondo IDMONDO:0029135
OMIM618135
DOIDDOID:0112382
UMLSC4748320
MedGen1648468
GARD0016294
Is cancer (heuristic)no

Also known as: LGMD-POMGNT2 related myopathy · MDDGC8

Data availability: 14 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disordercongenital nervous system disordercongenital muscular dystrophymuscular dystrophy-dystroglycanopathymuscular dystrophy-dystroglycanopathy, type Cmuscular dystrophy-dystroglycanopathy (limb-girdle), type C, 8

Related subtypes (8): autosomal recessive limb-girdle muscular dystrophy type 2K, autosomal recessive limb-girdle muscular dystrophy type 2M, autosomal recessive limb-girdle muscular dystrophy type 2O, autosomal recessive limb-girdle muscular dystrophy type 2N, autosomal recessive limb-girdle muscular dystrophy type 2P, autosomal recessive limb-girdle muscular dystrophy type 2T, autosomal recessive limb-girdle muscular dystrophy type 2U, limb-girdle muscular dystrophy due to POMK deficiency

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

14 retrieved; paginated sample, class counts are floors:

5 uncertain significance, 2 benign, 2 benign/likely benign, 2 conflicting classifications of pathogenicity, 2 pathogenic, 1 likely pathogenic

ClinVarVariant (HGVS)GeneClassificationReview
545449NM_032806.6(POMGNT2):c.758C>T (p.Pro253Leu)POMGNT2Pathogeniccriteria provided, multiple submitters, no conflicts
565308NM_032806.6(POMGNT2):c.494T>C (p.Met165Thr)POMGNT2Pathogenicno assertion criteria provided
3780481NM_032806.6(POMGNT2):c.1264C>T (p.Gln422Ter)POMGNT2Likely pathogeniccriteria provided, single submitter
37208NM_032806.6(POMGNT2):c.473G>A (p.Arg158His)POMGNT2Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
627559NM_032806.6(POMGNT2):c.511G>A (p.Asp171Asn)POMGNT2Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
1010449NM_032806.6(POMGNT2):c.1681C>T (p.Arg561Cys)POMGNT2Uncertain significancecriteria provided, multiple submitters, no conflicts
1450409NM_032806.6(POMGNT2):c.1385G>A (p.Arg462Gln)POMGNT2Uncertain significancecriteria provided, multiple submitters, no conflicts
2161912NM_032806.6(POMGNT2):c.1682G>A (p.Arg561His)POMGNT2Uncertain significancecriteria provided, multiple submitters, no conflicts
2444502NM_032806.6(POMGNT2):c.255C>G (p.Cys85Trp)POMGNT2Uncertain significancecriteria provided, single submitter
540489NM_032806.6(POMGNT2):c.377A>G (p.Asn126Ser)POMGNT2Uncertain significancecriteria provided, multiple submitters, no conflicts
262102NM_032806.6(POMGNT2):c.-43C>TPOMGNT2Benigncriteria provided, multiple submitters, no conflicts
262104NM_032806.6(POMGNT2):c.1365G>A (p.Pro455=)POMGNT2Benigncriteria provided, multiple submitters, no conflicts
262105NM_032806.6(POMGNT2):c.1488C>T (p.Gly496=)POMGNT2Benign/Likely benigncriteria provided, multiple submitters, no conflicts
377356NM_032806.6(POMGNT2):c.1385G>T (p.Arg462Leu)POMGNT2Benign/Likely benigncriteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
POMGNT2Orphanet:899Walker-Warburg syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

SubsetGenes
multi_evidence1

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
POMGNT2HGNC:25902ENSG00000144647Q8NAT1Protein O-linked-mannose beta-1,4-N-acetylglucosaminyltransferase 2clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
POMGNT2Protein O-linked-mannose beta-1,4-N-acetylglucosaminyltransferase 2O-linked mannose beta-1,4-N-acetylglucosaminyltransferase that transfers UDP-N-acetyl-D-glucosamine to the 4-position of the mannose to generate N-acetyl-D-glucosamine-beta-1,4-O-D-mannosylprotein.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

FamilyGenesFoldFDR
Antibody/Immunoglobulin129.2×0.034

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
POMGNT2Antibody/Immunoglobulinyes2.4.1.312FN3_dom, Glycosyltransferase_61, Ig-like_fold

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)1
unknown0

Top tissues across cohort

TissueCohort genes
cardiac muscle of right atrium1
lateral nuclear group of thalamus1
right hemisphere of cerebellum1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
POMGNT2245ubiquitousmarkerlateral nuclear group of thalamus, right hemisphere of cerebellum, cardiac muscle of right atrium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

SymbolInteractor count
POMGNT2968

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
POMGNT2Q8NAT13

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
DAG1 core M3 glycosylations11903.3×5e-04POMGNT2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
protein O-linked glycosylation via mannose1936.2×0.003POMGNT2
protein O-linked glycosylation1224.7×0.007POMGNT2
neuron migration1133.8×0.007POMGNT2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

SymbolMoleculesMax phase
POMGNT200

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
POMGNT22.4.1.312protein O-mannose beta-1,4-N-acetylglucosaminyltransferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

TierDefinitionGenesSymbols
AApproved (phase 4 drug)0
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug1POMGNT2
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

SymbolChEMBL assaysDrugged partners (top 3)
POMGNT20

Clinical trials & evidence

Clinical trials

Clinical trials: 0.